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Details on Person UniProt:Q8N668 COMMD1

Class:Id	ReferenceGeneProduct:145834
_chainChangeLog	initiator methionine:1 added on Fri February 6 2015;chain:2-190 added on Fri February 6 2015;initiator methionine:1 for 145834 removed on Fri Nov 03 2023;initiator methionine: for 145834 added on Fri Nov 03 2023;initiator methionine: for 145834 removed on Fri Aug 15 2025;initiator methionine:1 for 145834 added on Fri Aug 15 2025
_displayName	UniProt:Q8N668 COMMD1
_timestamp	2025-08-15 21:06:12
chain	initiator methionine:1 chain:2-190
checksum	9C810AECA67011DC
comment	FUNCTION Scaffold protein in the commander complex that is essential for endosomal recycling of transmembrane cargos; the commander complex is composed of the CCC subcomplex and the retriever subcomplex (PubMed:37172566, PubMed:38459129). Can modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes by displacing CAND1; in vitro promotes CRL E3 activity and dissociates CAND1 from CUL1 and CUL2 (PubMed:21778237). Promotes ubiquitination of NF-kappa-B subunit RELA and its subsequent proteasomal degradation. Down-regulates NF-kappa-B activity (PubMed:15799966, PubMed:17183367, PubMed:20048074). Involved in the regulation of membrane expression and ubiquitination of SLC12A2 (PubMed:23515529). Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits and by promoting their ubiquitination presumably involving NEDD4L. Promotes the localization of SCNN1D to recycling endosomes (PubMed:14645214, PubMed:20237237, PubMed:21741370). Promotes CFTR cell surface expression through regulation of its ubiquitination (PubMed:21483833). Down-regulates SOD1 activity by interfering with its homodimerization (PubMed:20595380). Plays a role in copper ion homeostasis. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes (PubMed:25355947). Can bind one copper ion per monomer (PubMed:17309234). May function to facilitate biliary copper excretion within hepatocytes. Binds to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (PubMed:18940794). Involved in the regulation of HIF1A-mediated transcription; competes with ARNT/Hif-1-beta for binding to HIF1A resulting in decreased DNA binding and impaired transcriptional activation by HIF-1 (PubMed:20458141). Negatively regulates neuroblastoma G1/S phase cell cycle progression and cell proliferation by stimulating ubiquitination of NF-kappa-B subunit RELA and NF-kappa-B degradation in a FAM107A- and actin-dependent manner (PubMed:28604741).SUBUNIT Component of the commander complex consisting of the CCC subcomplex and the retriever subcomplex (PubMed:37172566, PubMed:38459129, PubMed:25355947, PubMed:28892079, PubMed:15799966). Component of the CCC (COMMD/CCDC22/CCDC93) subcomplex consisting of COMMD1, COMMD2, COMMD3, COMMD4, COMMD5, COMMD6, COMMD7, COMMD8, COMMD9, COMMD10, CCDC22 and CCDC93; within the complex forms a heterodimer with COMMD6 (PubMed:37172566, PubMed:38459129, PubMed:15799966, PubMed:23563313, PubMed:25355947, PubMed:28892079). Interacts with VPS35L; the interaction associates the CCC complex with the retriever complex (PubMed:25355947, PubMed:28892079). Identified in a complex with an E3 ubiquitin ligase complex composed of TCEB1/elongin C, CUL2, SOCS1 and RBX1; in the complex interacts directly with SOCS1 and CUL2 (PubMed:17183367). Identified in a complex with NF-kappa-B (PubMed:16573520). Interacts directly with SLC12A2 (PubMed:23515529). Interacts directly with ATP7B (via the N-terminal region) (PubMed:12968035, PubMed:17919502). Interacts with ATP7A (PubMed:21667063). Interacts with FAM107A; this interaction stabilizes COMMD1 in the nucleus (PubMed:28604741). Interacts with CCS, CDKN2A, RELA, REL, RELB, NFKB1/p105, NFKB2/p100, NFKBIB, SCNN1D, SCNN1B, CFTR, CLU, SGK1, AKT1, CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5, CUL7, HIF1A (PubMed:14645214, PubMed:16573520, PubMed:18305112, PubMed:20237237, PubMed:20595380, PubMed:20458141, PubMed:20068069, PubMed:21778237, PubMed:21483833, PubMed:23637203, PubMed:23563313, PubMed:25074812).INTERACTION Shuttles between nucleus and cytosol. Detected in perinuclear foci that may be aggresomes containing misfolded, ubiquitinated proteins.ALTERNATIVE PRODUCTS Ubiquitous. Highest expression in the liver, with lower expression in brain, lung, placenta, pancreas, small intestine, heart, skeletal muscle, kidney and placenta. Down-regulated in cancer tissues.PTM Acetylated by EP300 ina stimuli-specific manner; protecting it from XIAP-mediated proteasomal degradation and required for interaction with RElA in response to stress.PTM Ubiquitinated; undergoes both 'Lys-63'- and 'Lys-48'-linked polyubiquitination. Ubiquitinated by XIAP, leading to its proteasomal degradation.SIMILARITY Belongs to the COMM domain-containing protein 1 family.
created	[InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10
description	recommendedName: COMM domain-containing protein 1 alternativeName: Protein Murr1
geneName	COMMD1 C2orf5 MURR1
identifier	Q8N668
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Alternative splicing Copper Cytoplasm Cytoplasmic vesicle Endosome Lipid-binding Membrane Metal-binding Nucleus Protein transport Proteomics identification Reference proteome Transcription Transcription regulation Transport Ubl conjugation Ubl conjugation pathway
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
name	COMMD1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8962268] ENSEMBL:ENSG00000173163 COMMD1 [Homo sapiens]
secondaryIdentifier	COMD1_HUMAN B4DFQ4 Q96GS0
sequenceLength	190
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:8975052] UniProt:Q8N668-1 COMMD1 [Homo sapiens] [ReferenceIsoform:8975053] UniProt:Q8N668-2 COMMD1 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:8955094] COMMD1 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:8955110] COMMD1 [cytosol] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:Q8N668 COMMD1 (145834)